Electroporation delivery systems and methods of using electroporation delivery systems

ABSTRACT

The present disclosure relates generally to electroporation systems and utilizing algorithms for electroporation pulse delivery including a patient&#39;s EKG/EGM monitoring. In some embodiments, an electroporation delivery system may include an electrocardiogram operatively connected to a processing device and a memory. One or more sensors may be operatively connected to the electrocardiogram for measuring electrical activity QRS complex of a patient&#39;s heart. One or more electrodes for treatment may be disposed in, at, or near the patient&#39;s heart, the one or more electrodes operatively connected to a pulse delivery mechanism. The electroporation delivery system may be configured to determine whether an electroporation pulse is deliverable to a patient based on the electrocardiogram.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a non-provisional application of, and claims thebenefit of priority to, U.S. Provisional Application Ser. No.62/549,631, filed Aug. 24, 2017, entitled “Electroporation DeliverySystems and Methods of Using Electroporation Delivery Systems,” theentirety of which application is expressly incorporated by referenceherein.

FIELD

The present disclosure relates generally to electroporation systems,including reversible electroporation (RE) and irreversibleelectroporation (IRE) systems and methods for using electroporationsystems and, more particularly, to utilizing algorithms forelectroporation pulse delivery including a patient's EKG/EGM monitoring.

BACKGROUND

Reversible electroporation (RE) may be typically used for drug deliveryto a selected tissue area by applying direct-current through electrodes.Irreversible electroporation (IRE) is typically used as a soft tissueablation technique (e.g., tumor removal) by delivering direct-currentenergy in short pulses to the selected tissue. For patients with healthyheart rhythms, undergoing an electroporation procedure near the heart isgenerally acceptable, as the electroporation procedure may rely on analgorithm that utilizes the QRS complex to determine when a pulse isdelivered to the patient (FIG. 1A). However, in a patient having anarrhythmia, for example, the Q wave, R wave, and/or the S wave may beuneven and irregular (e.g., a patient's heart rate may be irregularand/or faster than normal heart rates) (FIG. 1B). The algorithmscurrently utilized in electroporation systems do not take into accountirregular QRS wave patterns, which could result in an electroporationpulse being delivered that may affect the QRS wave.

For example, when an electroporation pulse is delivered at less than orequal to 1.7 cm from the heart, a patient may experience a fatal (major)event. Even when an electroporation pulse is delivered at a distancegreater than 1.7 cm from the heart, a patient may experience a minorevent. Known algorithms typically issue a pulse within a certain timeframe after the R wave. As can be seen in FIG. 1A, an electroporationpulse signal sent during an R wave in a regular heartbeat may bedelivered prior to the T wave in the refractory period, while FIG. 1Billustrates that an irregular heartbeat may have a wider R wave, therebyresulting in a pulse occurring during the T wave. If an electroporationpulse is delivered during the T wave, a patient may experience malignantatrial and ventricular arrhythmias. In some instances, up to 14% ofelectroporation cases may cause ventricular fibrillation.

It is with respect to these and other considerations that the presentimprovements may be useful.

SUMMARY

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to necessarily identify keyfeatures or essential features of the claimed subject matter, nor is itintended as an aid in determining the scope of the claimed subjectmatter.

According to an exemplary embodiment of the present disclosure, anelectroporation delivery system may include an electrocardiogramoperatively connected to a processing device and a memory, one or moresensors operatively connected to the electrocardiogram for measuringelectrical activity QRS complex of a patient's heart, and one or moreelectrodes for treatment at, in, or near the patient's heart, the one ormore electrodes operatively connected to a pulse delivery mechanism. Theelectroporation delivery system may be configured to determine whetheran electroporation pulse is deliverable to a patient based on theelectrocardiogram.

According to an exemplary embodiment of the present disclosure, a methodfor delivering an electroporation pulse by an electroporation deliverysystem for treatment in, at, or near a patient's heart may includemeasuring electrical activity QRS complex of the patient's heart by anelectrocardiogram and one or more sensors operatively connected to aprocessing device and a memory, calculating by the processing device arolling average by averaging a series of four pulse parameters,comparing the rolling average to a determined value, and delivering anelectroporation pulse by one or more electrodes operatively connected toa pulse delivery mechanism of the electroporation delivery system inresponse to the rolling average being equal to the determined value.

According to an exemplary embodiment of the present disclosure, a systemfor delivering an electroporation pulse by an electroporation deliverysystem for treatment in, at, or near a patient's heart may be configuredto execute steps that include measuring electrical activity QRS complexof the patient's heart by an electrocardiogram and one or more sensorsoperatively connected to a processing device and a memory, calculatingby the processing device a rolling average by averaging a series of fourpulse parameters, comparing the rolling average to a determined value,and delivering an electroporation pulse by one or more electrodesoperatively connected to a pulse delivery mechanism of theelectroporation delivery system in response to the rolling average beingequal to the determined value.

In various of the foregoing and other embodiments of the presentdisclosure the processing device may be configured to execute thefollowing steps including measuring and averaging approximately 30initial heartbeat durations of the patient's heart, calculating arolling average by averaging a series of four heartbeat durations, andcomparing the rolling average to the averaged initial heartbeatdurations including a standard deviation. If the rolling average isequal to the average initial heartbeat durations within the standarddeviation, the electroporation delivery system may deliver theelectroporation pulse during a fifth heartbeat duration following theaveraged series of four heartbeat durations, and if the rolling averageis not equal to the average initial heartbeat durations within thestandard deviation, the electroporation delivery system may not deliverythe electroporation pulse during the fifth heartbeat duration followingthe averaged series of four heartbeat durations.

In various of the foregoing and other embodiments of the presentdisclosure the processing device may be configured to execute thefollowing steps: (a) calculating a rolling average by averaging a seriesof four heartbeat durations, (b) setting the rolling average to aheartbeat average including a standard deviation, and (c) comparing therolling average to a fifth heartbeat duration following the averagedseries of four heartbeat durations. If the fifth heartbeat durationfollowing the averaged series of four heartbeat durations is equal tothe rolling average within the standard deviation, the electroporationdelivery system may deliver the electroporation pulse during a sixthheartbeat duration following the fifth heartbeat duration, and if thefifth heartbeat duration following the averaged series of the fourheartbeat durations is not equal to the rolling average within thestandard deviation, the electroporation delivery system may not deliverthe electroporation pulse during the sixth heartbeat duration followingthe fifth heartbeat duration. The steps (a)-(c) may be repeatable untilat least one of: (i) delivery of electroporation pulses is complete; and(ii) after a predetermined number of electroporation pulses are notdelivered during the following fifth or sixth heartbeat duration, theelectroporation delivery system is stopped. Delivery of theelectroporation pulse during the sixth heartbeat duration may occur at atime determined by the averaged series of four heartbeat durationsdivided by two after a Q wave of the QRS complex of the sixth heartbeatduration.

In various of the foregoing and other embodiments of the presentdisclosure the processing device may be configured to execute thefollowing steps including measuring and averaging approximately 30initial R wave amplitudes in the QRS complex of the patient's heart,calculating a rolling average by averaging a series of four R waveamplitudes, and comparing the rolling average to the average initial Rwave amplitudes including a standard deviation. If the rolling averageis equal to the average initial R wave amplitudes within the standarddeviation, the electroporation delivery system may deliver theelectroporation pulse during a fifth heartbeat duration following theaveraged series of four R wave amplitudes. If the rolling average is notequal to the average initial R wave amplitudes within the standarddeviation, the electroporation delivery system may not deliver theelectroporation pulse during the fifth heartbeat duration following theaveraged series of four R wave amplitudes.

In various of the foregoing and other embodiments of the presentdisclosure, the processing device may be configured to execute thefollowing steps including calculating a rolling average by averaging aseries of four R wave amplitudes in the QRS complex of the patient'sheart, setting the rolling average to the averaged R wave amplitudesincluding a standard deviation, and comparing the rolling average to afifth R wave amplitude of a fifth heartbeat duration following theaveraged series of four R wave amplitudes. If the fifth R wave amplitudefollowing the averaged series of four R wave amplitudes is equal to therolling average within the standard deviation, the electroporationdelivery system may deliver the electroporation pulse during a sixthheartbeat duration following the fifth R wave amplitude. If the fifth Rwave amplitude following the averaged series of the four R waveamplitudes is not equal to the rolling average within the standarddeviation, the electroporation delivery system may not deliver theelectroporation pulse during the sixth heartbeat duration following thefifth R wave amplitude.

In various of the foregoing and other embodiments of the presentdisclosure, the electroporation delivery system may be configured for atleast one of ablation and drug delivery. The electroporation pulse maybe deliverable by the electroporation delivery system within 50 ms ofthe R wave of the fifth heartbeat duration. The electroporation pulsemay be deliverable by the electroporation delivery system after 50 ms ifan average distance between an S wave and a T wave of the QRS complex isgreater than 50 ms plus two additional electroporation pulse durations.

In various of the foregoing and other embodiments of the presentdisclosure, the electroporation delivery may include one or more signalfilters for extracting at least one of an R wave and a T wave of the QRScomplex. The electroporation pulse may be deliverable in response to apositive value of the R wave and a negative value of the T wave outputfrom the one or more filters. The electroporation pulse may notdeliverable in response to a positive value of the R wave and a positivevalue of the T wave output from the one or more filters. Theelectroporation pulse may be deliverable in response to the R wave beingwithin 70 ms and the negative value of the T wave output from the one ormore filters. The electroporation pulse shape may be at least one ofsquare-shaped and defibrillation-like shaped. The electroporation pulseshape may be at least one of monopolar and bipolar. The electroporationdelivery system may be operational for treating at least one of atrialfibrillation and cancer disposed in, at, or near the heart.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that pacing of the patient'sheart may be adjustable for electroporation pulse delivery by inducedpacing, including the following steps including pacing a portion of thepatient's heart, detecting an evoked potential, wherein if no evokedpotential is detected, the pacing of the portion of the patient's heartmay be continued and no electroporation pulse may be delivered, and inresponse to detecting evoked potential, determining if the detectionoccurs during a vulnerable period of a T wave, wherein in response tothe detection occurring during the vulnerable period of the T wave, thepacing of the portion of the patient's heart may be continued and noelectroporation pulse may be delivered, and wherein in response to thedetection not occurring during the vulnerable period of the T wave, theelectroporation pulse may be delivered. Pacing of the patient's heartmay be adjustable for electroporation pulse delivery by at leastcontinuous pacing, including the following steps including (a) sending acontinuous pacing signal to the patient's heart to maintain the heart ina contracted state, (b) during the continuous pacing, delivering one ormore electroporation pulses, and (c) monitoring heart rhythms of thepatient for irregularities, wherein in response to detecting anirregularity, pacing the patient's heart to a normal rhythm; and whereinin response to detecting a regular heartbeat, steps (a), (b), and (c)may be repeated if additional treatment is needed. Pacing of thepatient's heart may be adjustable for electroporation pulse delivery byat least administering a drug dosage for adjusting the pace of thepatient's heart. Electroporation pulse delivery may be paused formonitoring the electrocardiogram for heart rhythms.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that the processing devicemay be configured to execute the following steps including measuring andaveraging approximately 30 initial heartbeat durations of the patient'sheart, calculating a rolling average by averaging a series of fourheartbeat durations, and comparing the rolling average to the averagedinitial heartbeat durations including a standard deviation. If therolling average is equal to the average initial heartbeat durationswithin the standard deviation, the electroporation pulse may bedeliverable during a fifth heartbeat duration following the averagedseries of four heartbeat durations. If the rolling average is not equalto the average initial heartbeat durations within the standarddeviation, the electroporation pulse may not be deliverable during thefifth heartbeat duration following the averaged series of four heartbeatdurations.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that the processing devicemay be configured to execute the following steps including calculating arolling average by averaging a series of four heartbeat durations,setting the rolling average to a heartbeat average including a standarddeviation, and comparing the rolling average to a fifth heartbeatduration following the averaged series of four heartbeat durations. Ifthe fifth heartbeat duration following the averaged series of fourheartbeat durations is equal to the rolling average within the standarddeviation, an electroporation pulse may be deliverable during a sixthheartbeat duration following the fifth heartbeat duration. If the fifthheartbeat duration following the averaged series of the four heartbeatdurations is not equal to the rolling average within the standarddeviation, the electroporation pulse may not be deliverable during thesixth heartbeat duration following the fifth heartbeat duration.Delivery of the electroporation pulse during the sixth heartbeatduration may occur at a time determined by the averaged series of fourheartbeat durations divided by two after a Q wave of the QRS complex ofthe sixth heartbeat duration.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that the processing devicemay be configured to execute the following steps including measuring andaveraging approximately 30 initial R wave amplitudes in the QRS complexof the patient's heart, calculating a rolling average by averaging aseries of four R wave amplitudes, and comparing the rolling average tothe average initial R wave amplitudes including a standard deviation. Ifthe rolling average is equal to the average initial R wave amplitudeswithin the standard deviation, the electroporation pulse may bedeliverable during a fifth heartbeat duration following the averagedseries of four R wave amplitudes. If the rolling average is not equal tothe average initial R wave amplitudes within the standard deviation, theelectroporation pulse may not be deliverable during the fifth heartbeatduration following the averaged series of four R wave amplitudes.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that the processing devicemay be configured to execute the following steps including calculating arolling average by averaging a series of four R wave amplitudes in theQRS complex of the patient's heart, setting the rolling average to theaveraged R wave amplitudes including a standard deviation, and comparingthe rolling average to a fifth R wave amplitude of a fifth heartbeatduration following the averaged series of four R wave amplitudes. If thefifth R wave amplitude following the averaged series of four R waveamplitudes is equal to the rolling average within the standarddeviation, the electroporation pulse may be deliverable during a sixthheartbeat duration following the fifth R wave amplitude. If the fifth Rwave amplitude following the averaged series of the four R waveamplitudes is not equal to the rolling average within the standarddeviation, the electroporation pulse may not be deliverable during thesixth heartbeat duration following the fifth R wave amplitude.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include one or more signal filtersfor extracting at least one of an R wave and a T wave of the QRScomplex. The electroporation pulse may be deliverable in response to apositive value of the R wave and a negative value of the T wave outputfrom the one or more filters. The electroporation pulse may not bedeliverable in response to the positive value of the R wave and apositive value of the T wave output from the one or more filters. Theelectroporation pulse may be deliverable in response to the R wave beingwithin 70 ms and the negative value of the T wave output from the one ormore filters.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that pacing of the patient'sheart may be adjustable for electroporation pulse delivery by inducedpacing, including the following steps including pacing a portion of thepatient's heart, detecting an evoked potential, wherein if no evokedpotential is detected, the pacing of the portion of the patient's heartmay be continued and no electroporation pulse may be delivered, and inresponse to detecting evoked potential, determining if the detectionoccurs during a vulnerable period of a T wave. In response to thedetection occurring during the vulnerable period of the T wave, thepacing of the portion of the patient's heart may be continued and noelectroporation pulse may be delivered. In response to the detection notoccurring during the vulnerable period of the T wave, theelectroporation pulse may be delivered. Pacing of the patient's heartmay be adjustable for electroporation pulse delivery by continuouspacing, including the following steps including (a) sending a continuouspacing signal to the patient's heart to maintain the heart in acontracted state, (b) during the continuous pacing, delivering one ormore electroporation pulses, and (c) monitoring heart rhythms of thepatient for irregularities. In response to detecting an irregularity,the patient's heart may be paced to a normal rhythm, and in response todetecting a regular heartbeat, steps (a), (b), and (c) may be repeatedif additional treatment is needed. Electroporation pulse delivery may bepaused for monitoring the electrocardiogram for regular heart rhythms.An electroporation pulse shape may be at least one of square-shaped anddefibrillation-like shaped. The electroporation pulse shape may be atleast one of monopolar and bipolar. The electroporation delivery systemmay be operational for treating at least one of atrial fibrillation andcancer disposed in, at, or near the heart.

In various of the foregoing and other embodiments of the presentdisclosure, systems and methods may include that the determined valuemay be a fifth heartbeat parameter following the averaged series of fourheartbeat parameters, and the rolling average may be set to a heartbeataverage including a standard deviation. In each of the foregoing andother embodiments of the present disclosure, systems and methods mayfurther comprise delivering the electroporation pulse during a fifthheartbeat duration following the averaged series of four heartbeatparameters, and not delivering the electroporation pulse during thefifth heartbeat duration following the averaged series of four heartbeatparameters in response to the rolling average not equaling thedetermined value. In each of the foregoing and other embodiments of thepresent disclosure, systems and methods may further comprise deliveringthe electroporation pulse during a sixth heartbeat duration following afifth heartbeat duration, and not delivering the electroporation pulseduring the sixth heartbeat duration following the fifth heartbeatduration in response to the fifth heartbeat parameter not equaling therolling average within the standard deviation. A heartbeat parameter maybe at least one of a heartbeat duration and an R wave amplitude. In eachof the foregoing and other embodiments of the present disclosure,systems and methods may further comprise adjusting a pace of thepatient's heart at least one of before, during, and after delivering theelectroporation pulse.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present disclosure are described by wayof example with reference to the accompanying figures, which areschematic and not intended to be drawn to scale. In the figures, eachidentical or nearly identical component illustrated is typicallyrepresented by a single numeral. For purposes of clarity, not everycomponent is labeled in every figure, nor is every component of eachembodiment shown where illustration is not necessary to allow those ofordinary skill in the art to understand the disclosure. In the figures:

FIG. 1A illustrates a QRS complex wave of a healthy heart;

FIG. 1B illustrates an irregular QRS complex wave of an unhealthy heart;

FIG. 2A illustrates an exemplary series of QRS complex wave monitoringin accordance with the present disclosure;

FIG. 2B illustrates a flow chart of an exemplary algorithm forelectroporation pulse delivery based on FIG. 2A;

FIG. 2C illustrates a flow chart of another exemplary algorithm forelectroporation pulse delivery based on FIG. 2A;

FIG. 3A illustrates another exemplary series of QRS complex wavemonitoring in accordance with the present disclosure;

FIG. 3B illustrates a flow chart of an exemplary algorithm forelectroporation pulse delivery based on FIG. 3A;

FIG. 3C illustrates a flow chart of an exemplary algorithm forelectroporation pulse delivery based on FIG. 3A;

FIG. 4 illustrates another exemplary series of QRS complex wavemonitoring using filters in accordance with the present disclosure;

FIG. 5 illustrates a flow chart of an exemplary embodiment of a methodfor pacing a patient's heart for electroporation pulse delivery inaccordance with the present disclosure;

FIG. 6 illustrates another flow chart of an exemplary embodiment of amethod for pacing a patient's heart for electroporation pulse deliveryin accordance with the present disclosure;

FIG. 7 illustrates an exemplary embodiment of a wave pulse shape inaccordance with the present disclosure;

FIG. 8 illustrates another exemplary embodiment of a wave pulse shape inaccordance with the present disclosure;

FIG. 9 illustrates an exemplary embodiment of an electroporationdelivery system and components in accordance with the presentdisclosure;

FIG. 10 illustrates an exemplary embodiment of a processing device of anelectroporation delivery system in accordance with the presentdisclosure;

FIG. 11 illustrates an exemplary embodiment of a storage medium of anelectroporation delivery system in accordance with the presentdisclosure; and

FIG. 12 illustrates an exemplary embodiment of a computing architectureof an electroporation delivery system in accordance with the presentdisclosure.

DETAILED DESCRIPTION

The present disclosure is not limited to the particular embodimentsdescribed herein. The terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting beyond the scope of the appended claims. Unless otherwisedefined, all technical terms used herein have the same meaning ascommonly understood by one of ordinary skill in the art to which thedisclosure belongs.

As used herein, the singular forms “a,” “an,” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” or “includes” and/or “including” when used herein,specify the presence of stated features, regions, steps elements and/orcomponents, but do not preclude the presence or addition of one or moreother features, regions, integers, steps, operations, elements,components and/or groups thereof.

One challenge with using a running template of QRS morphology may bewhen a heart rhythm has changed to an arrhythmia prior to starting thecount for which electroporation may be delivered. The QRS morphology maychange significantly as energy is delivered, although it may not bedisadvantageous and may not even necessitate stoppage of energydelivery. One possible way to get around this is incorporation of anexisting template that is annotated by a user stating template 1-normal(e.g., FIG. 1A) and template 2-targeted arrhythmia (e.g., FIG. 1B). Ifthe QRS complex stays in template 1, then energy may continue to bedelivered. If the QRS complex transitions from template 2 to template 1,then energy may continue to be delivered. However, if any change to aQRS other than template 1 or 2 is seen, then energy delivery may bestopped because the patient may be experiencing a pro-arrhythmia, or areference point may no longer be reliable for timing of energy delivery.

As mentioned above with respect to FIG. 1A, the QRS complex illustratesa heart rate signal seen in a typical electrocardiogram (EGM, EKG) of ahealthy patient (e.g., a normal heart rhythm). By issuing anelectroporation pulse to occur during the absolute refractory period,for example, between the S wave and the T wave, external stimuli areincapable of inducing action potential, thereby preventing malignantarrhythmias. In some embodiments, an electroporation pulse may include areversible electroporation (RE) pulse, and an irreversibleelectroporation (IRE) pulse. Additionally, an electroporation pulse maybe one or more square wave pulses delivered during the refractoryperiod, between each heartbeat. An algorithm may generate a pulse 50 msafter the Q wave. However, when a patient has an irregular heartbeatsignal (e.g., an abnormal or irregular heart rhythm), as illustrated inFIG. 1B, a pulse generated 50 ms after the Q wave may occur during the Twave and potentially increase a patient's risk of injury. To account forirregular heartbeats, an algorithm may instead be used that includes arolling average of a patient's electrocardiogram to determine when tosend an electroporation pulse. Exemplary embodiments of algorithms inaccordance with the present disclosure may be used with an internalelectrocardiogram (e.g., via at least one of a coronary sinus (CS)catheter, pacemaker, and electroporation device, such as a reversible(RE) or irreversible (IRE) device) and/or a 3-lead, 12-lead, or amodified 12-lead external electrocardiogram.

The systems and methods described herein are intended to overcome thedisadvantages in existing electroporation delivery systems by monitoringEKG, EGM wave signals and only delivering a pulse if selected conditionsare satisfied. If the selected conditions have not been met than theelectroporation delivery system will not send a pulse signal. This helpsto ensure patient safety, in particular for patients with arrhythmias orother heart conditions that may result in an irregular heart rate. Asmentioned above, if a pulse is to be delivered at, in, and/or near theheart (where “near the heart” may be less than or equal to 1.7 cm fromthe heart), an electroporation pulse being delivered at an incorrectportion of the EKG/EGM signal may be fatal in a patient. So that anelectroporation delivery system may be used for treatment in humans,pulse delivery triggering algorithms are needed to provide a safe andreliable delivery method. For example, treatment may include energydelivery for ablation of tumors or other malignancies in IRE deliverysystems, and/or drug delivery in RE delivery systems. Including anelectroporation pulse delivery algorithm, such as the algorithmsdescribed herein, is not intended to limit the electroporation deliverysystem's ability to cause energy delivery in the selected area of thepatient but to restrict undesirable energy delivery at selected pointsof the QRS wave complex. For example, an electroporation delivery systemutilizing a delivery algorithm in accordance with the present disclosuremay be utilized for treating at least one of atrial fibrillation andesophageal cancer or other cancers located around and near the heartwithout causing negative effects to a patient's heart during pulsedelivery.

An electroporation delivery system, such as an RE or IRE deliverysystem, of which an exemplary embodiment in accordance with the presentdisclosure is illustrated in the block diagram 900 of FIG. 9, mayincorporate the algorithms described herein. In some embodiments, anelectroporation delivery system 905 may include several components foroperation, including but not limited to a processing device 910, a powersource 915, a memory 920, an EKG/EGM 925, and a pulse delivery mechanism930, which are described below. It is understood that at least a portionof the EKG/EGM 925 may be an internal and/or an external component ofthe electroporation delivery system 905. In some embodiments, thealgorithms may be stored in the memory 920 for use by the processingdevice 910. The electroporation delivery system 905 may be operativelyconnected to one or more sensors 940, which may be attachable externallyto a patient and/or insertable at selected internal locations of thepatient, for measuring electrical activity of a patient's heart for theEKG/EGM 925. In some embodiments, the sensors 940 may be connected bywire connections, although the sensors 940 may be wirelessly connected.The electroporation delivery system 905 may also be operativelyconnected to one or more electrodes 935 for delivering pulses by thepulse delivery mechanism 930 in an electroporation treatment near thepatient's heart. The electrodes may be configured for delivery to theheart and application of an electroporation pulse, with deliveryplatforms, e.g., an electroporation balloon catheter, for delivery ofelectroporation energy to treat tumors and other malignancies that wouldotherwise require electrocardiogram gaiting to avoid induction ofarrhythmia. In some embodiments, individual electrodes may be placed ina retro-pericardial area around the heart.

In the following description, numerous specific details such asprocessor and system configurations are set forth in order to provide amore thorough understanding of the described embodiments. However, thedescribed embodiments may be practiced without such specific details.Additionally, some well-known structures, circuits, and the like havenot been shown in detail, to avoid unnecessarily obscuring the describedembodiments.

One or more flow charts for carrying out the executed steps/methods ofthe disclosure may be provided. Although such figures presented hereinmay include a particular process flow, it can be appreciated that theflow charts merely provide an example of how the general functionalityas described herein can be implemented. Further, the given flow chartsdo not necessarily have to be executed in the order presented unlessotherwise indicated. In addition, the given processes may be implementedby a hardware element, a software element executed by a processor, orany combination thereof. For example, the processes may be implementedby a processor component executing instructions stored on an article ofmanufacture, such as a storage medium. A storage medium may comprise anynon-transitory computer-readable medium or machine-readable medium, suchas an optical, magnetic or semiconductor storage. The storage medium maystore various types of computer executable instructions, such asinstructions to implement one or more disclosed processes. Examples of acomputer readable or machine readable storage medium may include anytangible media capable of storing electronic data, including volatilememory or non-volatile memory, removable or non-removable memory,erasable or non-erasable memory, writeable or re-writeable memory, andso forth. Examples of computer executable instructions may include anysuitable type of code, such as source code, compiled code, interpretedcode, executable code, static code, dynamic code, object-oriented code,visual code, and the like. The embodiments are not limited in thiscontext.

Referring now to FIG. 2A, a diagram of a series of QRS complex waves 200of a patient's heartbeat over time are illustrated, and FIG. 2B,illustrating a flow chart 240 of an algorithm for use with anelectroporation delivery system 905 (e.g., FIG. 9) of an exemplaryembodiment in accordance with the present disclosure. The algorithmsdescribed herein may provide methods for operating an electroporationdelivery system to deliver an electroporation pulse based on a patient'sEKG/EGM. An algorithm used in an electroporation delivery system inaccordance with an exemplary embodiment of the present disclosure mayobtain a determined value, for example, by calculating an average x forapproximately 30 initial pulse durations (ms), e.g., heartbeatdurations, within a standard deviation a, at step 242. In someembodiments, a 95% confidence interval may be used, or (1.96×standarddeviation)/√{square root over (4)}, or 0.98*stdev. Althoughapproximately 30 heartbeat durations may be measured, which may bemeasured in approximately 30 seconds, an average x may optionally betaken for approximately 10 to 45 heartbeat durations, so that a medicalprofessional may still measure an average in under a minute beforestarting therapy. In other embodiments, the medical professional mayoptionally review the measured heartbeat durations, and approve thetotal number, or take additional measurements, before calculating theaverage.

(1) average ˜30 heartbeat durations=x±a

A rolling average may be calculated by averaging a series of four pulseparameters, for example, a series of four heartbeat durations may becalculated to determine if an electroporation pulse should be deliveredduring the following heartbeat duration. The four heartbeat durationsmay be measured independently of the pulses used for determining theaverage heartbeat durations, although in other embodiments the fourheartbeat durations may be included in the initial 30 heartbeatdurations used to determine the average heartbeat duration. In someembodiments, the series may be greater or fewer than four heartbeatdurations, although using fewer may be unusable if one is an irregularheartbeat. For example, heartbeat durations indicated at 202 area “C”,204 area “D”, 206 area “E”, 208 area “F”, 210 area “G”, and 212 area “H”illustrate exemplary heartbeat durations that may be used in calculatinga rolling average, in milliseconds (ms). For example, heartbeatdurations C, D, E, and F may be averaged to a first rolling average atstep 244:

$\begin{matrix}\frac{( {C + D + E + F} )}{4} & (2)\end{matrix}$

Step 246 may compare the determined value to the rolling average, todetermine that if a first rolling average of eq. (2) is equal to theaverage initial 30 heartbeat durations within a standard deviation a ineq. (1), then an electroporation pulse may be delivered in the fifthheartbeat duration following the averaged four heartbeat durations(e.g., C, D, E, F) during the absolute refractory period, e.g.,heartbeat duration 210 area “G”, as indicated at reference numeral 216at step 248. In some embodiments, software may delay delivery anddeliver a pulse in heartbeat duration 212 area “H”, skipping theheartbeat duration 210 area “G”, although it may be more advantageous todeliver the electroporation pulse during the heartbeat duration 210 area“G”.

(3) if

${\frac{( {C + D + E + F} )}{4} = {\overset{\_}{x} \pm a}},$

then pulse is delivered during G

However, if the first rolling average in eq. (2) is not equal to theaverage initial 30 heartbeat durations within a standard deviation a ineq. (1), then an electroporation pulse is not delivered in the fifthheartbeat duration following the average four heartbeat durations (e.g.,C, D, E, F) during the absolute refractory period at step 250. Thus, thealgorithm may consider an irregular heart rhythm and determine not todeliver the electroporation pulse during heartbeat duration 210 area“G”.

(4) if

${\frac{( {C + D + E + F} )}{4} \neq {\overset{\_}{x} \pm a}},$

then pulse is not delivered during G

The flow chart 240 illustrates that the process may continue bycalculating another rolling average at step 244. For example, a secondrolling average may next be calculated averaging heartbeat durations D,E, F, and G:

(5)

$\frac{( {D + E + F + G} )}{4}$

The second rolling average of eq. (5) may then be compared to eq. (1),so that if the second rolling average is equal to the average initial 30heartbeat durations within a standard deviation a at step 246, then anelectroporation pulse may be delivered in the fifth heartbeat durationfollowing the averaged four heartbeat durations (e.g., D, E, F, G)during the absolute refractory period, e.g., heartbeat duration 212 area“H”, as indicated at reference numeral 216 at step 248.

(6) if

${\frac{( {D + E + F + G} )}{4} = {\overset{\_}{x} \pm a}},$

then pulse is delivered during H

However, if the second rolling average in eq. (5) is not equal to theaverage initial 30 heartbeat durations within a standard deviation a ineq. (1), then an electroporation pulse is not delivered in the fifthheartbeat duration following the average four heartbeat durations (e.g.,D, E, F, G) during the absolute refractory period at step 250. This mayallow for large variances in the absolute refractory period as mentionedabove. Thus, the algorithm may consider an irregular heart rate anddetermine not to deliver the electroporation pulse during heartbeatduration 212 area “H”.

(7) if

${\frac{( {D + E + F + G} )}{4} \neq {\overset{\_}{x} \pm a}},$

then pulse is not delivered during H

Subsequent rolling averages may be calculated via steps 244, 246, 248and/or 250 until all electroporation pulses have been delivered. In someembodiments, the electroporation delivery system may determine thatafter a predetermined number of skipped heartbeat durations (e.g., therolling average is not equal to the initial heartbeat durations withinthe standard deviation), the procedure is stopped, and/or an alarm maybe generated.

Referring now to FIG. 3A, a diagram of a series of QRS complex waves 300over time are illustrated, and to FIG. 3B, illustrating a flow chart 346of an algorithm for use with an electroporation delivery system 905(e.g., FIG. 9) of an exemplary embodiment in accordance with the presentdisclosure. As described above with respect to FIGS. 2A-2B, an algorithmused in an electroporation delivery system in accordance with anexemplary embodiment of the present disclosure may calculate a rollingaverage by averaging a series of four heartbeat duration parameters,(e.g., pulse) including, for example, 302 area “B”, 304 area “C”, 306area “C”, 308 area “D”, 310 area “E”, 312 area “F”, 314 area “G”, and/or316 area “H”, which illustrate exemplary heartbeat durations inmilliseconds (ms). In a first rolling average, heartbeat durations B, C,D, and E may first be averaged at step 348:

(8)

$\frac{( {B + C + D + E} )}{4}$

This first rolling average calculated in eq. (8) may be set as aheartbeat duration average and within a standard deviation a′, x′±a′ atstep 350. In some embodiments a 95% confidence interval may be used, or(1.96×standard deviation)/√{square root over (4)}, or 0.98*stdev. Thefirst rolling average is then compared to the determined value at step352. In some embodiments, the determined value may be the followingheartbeat duration, e.g., the fifth heartbeat duration “F”. If the Fheartbeat duration is equal to the heartbeat duration average within thestandard deviation (e.g., ±0.98*stdev), then an electroporation pulsemay be delivered during the subsequent sixth heartbeat duration “G” atstep 354. In some embodiments, a combination of the amplitude and therolling average may be used to determine a correct wave peak is beingmeasured and whether the duration changes. In some embodiments, theelectroporation pulse may be delivered at x/2 ms after the Q wave of theG heartbeat duration indicated at reference numeral 312, where x is thefour heartbeat duration rolling average that will adjust as the rollingaverages continue. The rolling heartbeat duration average may help tomaintain and validate the triggering reference point on the QRS wavecomplex so that the pulse may be reliably delivered between the S and Twaves.

It may be assumed in some embodiments that the heartbeat duration isconsistent enough for short periods of time and is not erratic so thatif the rate of the heartbeat increases or decreases slowly, theelectroporation pulsing will not stop automatically because theheartbeat may still be within normal range even if the pace changes. Theelectroporation delivery system may recognize that the pace changes, andadjust the algorithms to pulse in the correct place. If the heartbeatbecomes irregular, e.g., an arrhythmia, the electroporation pulsedelivery system may recognize it immediately since the pulses will notbe within the rolling average range, so that the electroporationdelivery system may alert a medical professional. In some embodiments,a′ may be set as a constant in lieu of 0.98*stdev, which may provide amore consistent, and thereby safer, range.

(9) if

${\frac{( {B + C + D + E} )}{4} = {{{\overset{\_}{x}}^{\prime} \pm a^{\prime}} = F}},$

then pulse is delivered during G

However, if the F heartbeat duration is not equal to the rolling averagewithin the standard deviation, then a pulse is not delivered during theG heartbeat at step 356. Thus, the algorithm may consider an irregularheart rhythm and determine not to deliver the electroporation pulseduring 312 area “G”.

(10) if

${\frac{( {B + C + D + E} )}{4} = {{{\overset{\_}{x}}^{\prime} \pm a^{\prime}} \neq F}},$

then pulse is not delivered during G

The flow chart 346 illustrates that the process may continue bycalculating another rolling average at step 348. A second rollingaverage may be calculated, using heartbeat durations C, D, E, and F,which may be set as the average x″ including a standard deviation a″:

(11)

$\frac{( {C + D + E + F} )}{4} = {{\overset{\_}{x}}^{''} \pm a^{''}}$

The average calculated in eq. (11) may then be compared to subsequentfifth heartbeat duration G at step 352. If G is equal to the averagewithin the standard deviation (e.g., a 95% confidence interval may beused, or (1.96×standard deviation)/√{square root over (4)}, or0.98*stdev), then an electroporation pulse may be delivered duringheartbeat duration H, indicated at reference numeral 314 at step 354. Insome embodiments, the electroporation pulse may be delivered at x/2 msafter the Q wave of the heartbeat duration H.

(12) if

${\frac{( {C + D + E + F} )}{4} = {{{\overset{\_}{x}}^{''} \pm a^{''}} = G}},$

then pulse is delivered during H

However, if the heartbeat duration G is not equal to the rolling averagewithin the standard deviation, then an electroporation pulse is notdelivered during the heartbeat duration H at step 356. This may allowfor large variances in the absolute refractory period as mentionedabove.

(13) if

${\frac{( {C + D + E + F} )}{4} = {{{\overset{\_}{x}}^{''} \pm a^{''}} \neq G}},$

then pulse is not delivered during H

Subsequent rolling averages may be calculated via steps 348, 350, 352,354, and/or 356 until all electroporation pulses have been delivered. Insome embodiments, the electroporation delivery system may determine thatafter a predetermined number of skipped pulses (e.g., the rollingaverage within the standard deviation is not equal to the subsequentfifth heartbeat duration), the procedure is stopped, and/or an alarm maybe generated. For example, if more than two electroporation pulses failto be delivered (e.g., based on equations 10,13), a warning may be sentto an operator of the electroporation delivery system, so that theoperator may determine whether to continue the procedure. Theelectroporation delivery system may further be configured toautomatically shut-down operation after a predetermined number of missedheartbeats (e.g., four) if an operator fails to respond. This may beadvantageous to help ensure patient safety when an irregular heart rateis determined.

Another exemplary embodiment of an algorithm in accordance with thepresent disclosure, and illustrated by flow chart 252 of FIG. 2C andflow chart 358 of FIG. 3C may include utilizing an amplitude of the Rwave as the heartbeat parameter. For example, indicated at referencenumerals 218, 220, 222, 224, 226, and 228, an average amplitude may becalculated as a rolling average similar to equations (2), (5), and (8).At step 256 a first rolling average may be taken by averaging a seriesof the amplitudes of the R wave indicated at reference numerals 218 ofduration C, 220 of duration D, 222 of duration E, and 224 of duration F.If the rolling average is equal to the determined value at step 258, theelectroporation pulse may be delivered during the subsequent fifthheartbeat duration G (see FIGS. 2A-2C) at step 260. In some embodiments,the determined value may be an average of 30 initial amplitudes of Rwaves within a standard deviation (e.g., x±a, where a is the 95%confidence interval described above) calculated at step 254. If thecompared determined value and the averaged series of the pulse parameter(e.g., R wave amplitude) are not equal, then at step 262 noelectroporation pulse is delivered. Subsequent rolling averages may becalculated via steps 256, 258, 260, and/or 262 until all electroporationpulses have been delivered.

Averages may also be calculated as described similar to FIGS. 3A-3B, inthat at step 360 first rolling average may be taken by averaging aseries of heartbeat parameters (e.g., amplitudes of the R wave)indicated at reference numerals 320 of heartbeat duration B, 322 ofheartbeat duration C, 324 of heartbeat duration D, and 326 of heartbeatduration E, and setting it equal to the average amplitude within astandard deviation at step 362. If the average is equal to a determinedvalue (e.g., an amplitude 328 of heartbeat duration F) at comparisonstep 364, then an electroporation pulse may be delivered duringheartbeat duration G indicated by reference numeral 312 (see FIGS.3A-3C) at step 366, and if they are not equal, then at step 368 noelectroporation pulse is delivered. In some embodiments, theelectroporation pulse may be deliverable by an electroporation deliverysystem within 50 ms. Subsequent rolling averages may be calculated viasteps 360, 362, 364, 366, and/or 368 until all electroporation pulseshave been delivered.

If a pulse will be delivered after 50 ms, some embodiments may utilizean average distance from the S wave to the T wave to determine if adelivered pulse is safe 50 ms after the R wave. The distance from the Swave to the T wave, for example, is indicated at reference numerals 230,232, 234, 236, and 238 of FIG. 2A, or 334, 336, 338, 340, 342, and 344of FIG. 3A. If the averaged distance between the S and T waves isgreater than 50 ms plus two electroporation pulse durations (ms), andthe amplitude for the R wave is satisfied, then an electroporation pulsemay be delivered. Two pulse durations may be used as a standard offsetmeasurement to ensure one pulse may be delivered safely even if therefractory period is slightly faster. Using one heartbeat duration mayallow a pulse delivery on the T wave if the refractory period increases,thereby potentially causing an arrhythmia. More than two electroporationpulse durations may be excessive in the event of long pulse widths. Insome embodiments, instead of a constant two pulse durations, the offsetmay be the total time of pulse delivery per trigger multiplied by aconstant, e.g., 1.25, or 1.5.

An exemplary embodiment of an algorithm in accordance with the presentdisclosure may include an “And Statement” using filters for monitoringthe QRS wave, or the EKG/EGM, or in some embodiments, the EGM wave, if aCS catheter is used for internal measurements. The wave signal may besplit before entering a first filter A, or a second filter B. Thefilters A, B may reduce background noise to enhance the selected waveportions. For example, filter A may only detect the R wave, and filter Bmay only detect the T wave due to their different frequencies. Whendetecting noise it may be positive and while not detecting noise it maynegative. The filters A, B may be advantageous when an EKG/EGM is lessdistinguishable between the T and R waves. In some embodiments, the Afilter may extract the R wave (in a QRS wave), or G wave (in an EGMwave), and the B filter may extract the T wave. As shown in FIG. 4, anexemplary embodiment of a series of EKG/EGM wave signals 400 includes anR wave indicated at reference numeral 405 and a T wave indicated atreference numeral 410.

If the output of the A filter is positive, and the output of the Bfilter is negative, then an electroporation pulse may be delivered.However, if the output of the A filter is positive, and the output ofthe B filter is also positive, then the electroporation delivery systemwill not deliver a pulse. Both A and B may be negative during therefractory period for a pulse to be delivered. The pulse may bedelivered approximately 50 ms after the R wave is detected, if theoutput of the B filter is negative, to be safe for most heart rhythms.In some embodiments, a pulse may safely be delivered up to approximately70 ms after the R wave is detected, where the refractory period isapproximately 250 ms. In some embodiments, instead of a constant 70 ms,a pulse may be safely delivered by: an average refractory period of thepatient−1.25*pulse length, or 1.25*total number of pulses delivered pertrigger event. In some embodiments, as an additional safety feature,detecting the T wave may ensure the refractory period isn't changing sothat in the event the T wave (+) is detected, the delivery system isstopped. In some embodiments, an electroporation pulse may bedeliverable between the R wave and T wave by detecting a T wave'sabsence, e.g., filter B does not detect any wave presence. If a T waveis detected at any point during pulsing, the delivery system mayimmediately stop pulsing.

Some embodiments may induce pacing, for example, before electroporationpulse delivery, during electroporation pulse delivery, and/or afterelectroporation pulse delivery. Pacing may also be utilized for apatient having a regular heartbeat (e.g., a heartbeat having a QRS wavecomplex as illustrated in FIG. 1A) or irregular heartbeat (e.g., aheartbeat having a QRS wave complex as illustrated in FIG. 1B), and maybe applied to a portion of the patient's heart, e.g., a ventricularportion. It may be advantageous to use pacing for patients having any ofa fast, regular, or irregular heartbeat so that the refractory periodmay be controllable and it may be known exactly when to deliver a pulse.The heart rhythm may be monitored, e.g., by monitoring theelectrocardiogram (EKG, EGM), for a regular and/or irregular heartbeatand heart rate. Pacing may be advantageous because long pace intervalswill increase the refractory period, to safely deliver one to aplurality of electroporation pulses per heartbeat, thereby deliveringtherapy faster. In some embodiments, electroporation pulse delivery maybe between 1 and 100 between heartbeats. In some embodiments, a pacingsignal may be delivered so that a patient's heartbeat is adjusted, e.g.,slowed, and after a predetermined amount of time from delivery of thepacing signal, an electroporation pulse may be delivered. Pacing may beaccomplished via the right side ventricle of a patient's heart, althougha pharmaceutical drug dosage may be used in addition to or instead of toadjust, e.g., slow, the heart pace. In some embodiments, pacingsimulating a heartbeat may be applied continuously throughout aprocedure.

FIG. 5 illustrates a flow chart 500 of an exemplary process for pacingand delivery of an electroporation pulse. At step 505, a pacing signalis applied to a patient's heart to slow the heart rate. In someembodiments, the pacing signal may be applied continuously. At step 510,the electroporation delivery system may determine if an evokedpotential, an electrical potential recorded from the patient's nervoussystem, is detected. If not, the electroporation delivery system doesnot deliver an electroporation pulse at 515, and is looped back tocontinue pacing the patient's heart at step 505. If an evoked potentialhas been detected, at step 520 the electroporation delivery systemdetermines if the patient is in a vulnerable portion of the EKG/EGM wavesignal, in particular, in the vulnerable period of the T wave. If yes,then the electroporation delivery system does not deliver anelectroporation pulse at step 515 and is looped back to pacing thepatient's heart at step 505. If the patient is not in a vulnerableperiod of the T wave, the electroporation delivery system may deliver anelectroporation pulse within an absolute refractory period at step 525.A T wave is a period in the heart where different tissues repolarize atdifferent rate, which, as a result, may create a repolarizationgradient, and stimulation with direct current on cardiac tissue whensuch a gradient is present may promote (or nullify) the induction ofhighly malignant ventricular arrhythmias including a polymorphicventricular tachycardia and ventricular fibrillation.

In some embodiments, induced pacing may occur only prior toelectroporation pulse delivery, although other embodiments may includepacing a patient's heartbeat during and/or after electroporation pulsedelivery as well. Slowing the pace of a patient's heart by inducedpacing may be advantageous because it may elongate the refractoryperiod, thereby preventing undesirable heart rhythm side effects. Insome embodiments, pacing may be utilized with the “And Statement” asdescribed above with respect to FIG. 4, which may be advantageous toprovide more electroporation pulses, either in frequency, amount, oramplitude, to regulate heart rhythm by electroporating cardiac cells andstopping the circuit or triggering site for the patient's arrhythmia.

In some embodiments, a patient's heart may be continuously paced by theelectroporation delivery system, or an external pacing device. FIG. 6illustrates a flow chart 600 of an exemplary process for continuouspacing and electroporation pulse delivery. It may be advantageous tomonitor a heart rate continuously for the heart rate and anyirregularities, e.g., every other heartbeat duration, or a time periodof a couple seconds, so that the continuous pacing and electroporationpulse delivery process will be a continuous process of check and pulse.At 602, a continuous pacing signal may be directed to at least one ofthe right ventricle of the heart and the area of interest. Sending acontinuous pacing signal may result in the heart being in a prolongedcontracted state. In some instances, the contracted state may lastapproximately 1 to 15 seconds. While a patient's heart is in thecontracted state by the continuous pacing signal being sent at step 605,the electroporation delivery system may deliver one or moreelectroporation pulses. It may be advantageous to contract the heart bya continuous pacing signal, as in a contracted state, theelectroporation pulse may not cause irregular heartbeats. Inembodiments, a pacing signal may be delivered to a patient's heart forat least one of a predetermined amount of time and a predeterminednumber of pulses. At step 610, the patient's heart may be monitored bypausing, or stopping pacing to determine if there are any arrhythmias orif the heartbeat is regular. Pacing may be paused or otherwise stoppedso heart rhythms may be monitored for several heartbeats at step 615. Inembodiments, the monitoring may occur over at least one of apredetermined amount of time and a predetermined number of heartbeats.If the heartbeat is regular, the system may determine at step 620 ifadditional pulses are needed. If the heartbeat is irregular, then thedelivery system may pace the heart back into a normal rhythm at step625. Steps 615 and 625 may repeat until the heart has a normal rhythm.If additional treatment is needed, e.g., more electroporation pulsesshould be delivered, pacing may be continued so that additional pulsesmay be delivered to complete treatment by returning to step 602. Oncetreatment is complete, at step 630 the process may end. Slowing the paceof a patient's heart by continuous pacing may be advantageous because itmay keep it in a contracted state, thereby preventing theelectroporation pulses from causing undesirable heart rhythm sideeffects.

In some embodiments, electroporation pulse delivery may be paused orstopped for monitoring a patient's heart EKG/EGM. This may beadvantageous during a prolonged ablation treatment by theelectroporation delivery system, so that an operator or medicalprofessional may determine that the electroporation pulsing has notcaused the patient's heart to go into an arrhythmia. Upon confirmationthat the patient's heart rhythms are normal, the electroporationdelivery system may continue operation as needed.

The electroporation pulse may be any of a variety of shapes, and may bedetermined by electronics of the electroporation delivery system andtheir ability to control the release of energy. In some embodiments, theelectroporation delivery system may deliver a pulse having at least oneof a square-shaped as shown in FIG. 7, and a defibrillation-like wave asshown FIG. 8. Additionally, the square-shaped wave and thedefibrillation-like wave may be monopolar or bipolar. For example, FIG.7 illustrates a square-shaped monopolar wave pulse 700, and FIG. 8illustrates a defibrillation-like bipolar wave pulse 800. Inembodiments, the square wave pulse shape may be positive, negative,and/or a combination of positive and negative. The shape of theelectroporation pulse may affect a particular response in the patient'sheart. Although “a pulse” may be described herein, it is understood thatone or more square wave pulses may be delivered between each heartbeat.

Referring back to FIG. 9, the electroporation delivery system 905 mayexecute processing operations or logic for the monitoring of the patientand electroporation pulse delivery using the processing device 910. Theprocessing device 910 may comprise various hardware elements, softwareelements, or a combination of both. Examples of hardware elements mayinclude devices, logic devices, components, processors, microprocessors,circuits, processor circuits, circuit elements (e.g., transistors,resistors, capacitors, inductors, and so forth), integrated circuits,application specific integrated circuits (ASIC), programmable logicdevices (PLD), digital signal processors (DSP), field programmable gatearray (FPGA), memory units, logic gates, registers, semiconductordevice, chips, microchips, chip sets, and so forth. Examples of softwareelements may include software components, programs, applications,computer programs, application programs, system programs, softwaredevelopment programs, machine programs, operating system software,middleware, firmware, software modules, routines, subroutines,functions, methods, procedures, software interfaces, application programinterfaces (API), instruction sets, computing code, computer code, codesegments, computer code segments, words, values, symbols, or anycombination thereof. Determining whether an embodiment is implementedusing hardware elements and/or software elements may vary in accordancewith any number of factors, such as desired computational rate, powerlevels, heat tolerances, processing cycle budget, input data rates,output data rates, memory resources, data bus speeds and other design orperformance constraints, as desired for a given implementation.

In some embodiments, the electroporation delivery system 905 may executecommunications operations or determination of delivery anelectroporation pulse using a communications component (not shown). Thecommunications component may implement any well-known communicationstechniques and protocols, such as techniques suitable for use withpacket-switched networks (e.g., public networks such as the Internet,private networks such as an enterprise intranet, and so forth),circuit-switched networks (e.g., the public switched telephone network),or a combination of packet-switched networks and circuit-switchednetworks (with suitable gateways and translators). The communicationscomponent may include various types of standard communication elements,such as one or more communications interfaces, network interfaces,network interface cards (NIC), radios, wireless transmitters/receivers(transceivers), wired and/or wireless communication media, physicalconnectors, and so forth. By way of example, and not limitation,communication media may include wired communications media and wirelesscommunications media. Examples of wired communications media may includea wire, cable, metal leads, printed circuit boards (PCB), backplanes,switch fabrics, semiconductor material, twisted-pair wire, co-axialcable, fiber optics, a propagated signal, and so forth. Examples ofwireless communications media may include acoustic, radio-frequency (RF)spectrum, infrared and other wireless media.

Turning now to FIG. 10, illustrated is an example of an operatingenvironment, which may be used monitor and determine when to deliverelectroporation pulses to a patient, a system 102 may include a server110 and a processing device 105, which may be the same or similar to theelectroporation delivery system 905 of FIG. 9, coupled via a network140. Server 110 and processing device 105 may exchange data 130 vianetwork 140, and data 130 may include executable instructions 132 forexecution within processing device 105. In some embodiments, data 130may be include data values, executable instructions, and/or acombination thereof. In other embodiments, data 130 may include sensormetric data from the sensors 940 and electrode data from the electrodes935 of FIG. 9. Network 140 may be based on any of a variety (orcombination) of communications technologies by which signals may beexchanged, including without limitation, wired technologies employingelectrically and/or optically conductive cabling, and wirelesstechnologies employing infrared, radio frequency, and/or other forms ofwireless transmission.

In various embodiments, processing device 105 may incorporate aprocessor component 150, which may be the same or similar to theprocessing device 910 of FIG. 9, a storage 160, controls 125 (forinstance, manually-operable controls), a display 138 and/or a networkinterface 115 to couple the processing device 105 to the network 140.Processor component 150 may incorporate security credentials 180, asecurity microcode 178, metadata storage 135 storing metadata 136, asecurity subsystem 174, one or more processor cores 170, one or morecaches 172 and/or a graphics controller 176. Storage 160 may includevolatile storage 164, non-volatile storage 162, and/or one or morestorage controllers 165. Processing device 105 may include a controller120 (for example, a security controller) that may include securitycredentials 180. Controller 120 may also include one or more of theembodiments described herein for unified hardware acceleration of hashfunctions.

Volatile storage 164 may include one or more storage devices that arevolatile in as much as they require the continuous provision of electricpower to retain information stored therein. Operation of the storagedevice(s) of volatile storage 164 may be controlled by storagecontroller 165, which may receive commands from processor component 150and/or other components of processing device 105 to store and/orretrieve information therein, and may convert those commands between thebus protocols and/or timings by which they are received and other busprotocols and/or timings by which the storage device(s) of volatilestorage 164 are coupled to the storage controller 165. By way ofexample, the one or more storage devices of volatile storage 164 may bemade up of dynamic random access memory (DRAM) devices coupled tostorage controller 165 via an interface, for instance, in which row andcolumn addresses, along with byte enable signals, are employed to selectstorage locations, while the commands received by storage controller 165may be conveyed thereto along one or more pairs of digital serialtransmission lines.

Non-volatile storage 162 may be made up of one or more storage devicesthat are non-volatile inasmuch as they are able to retain informationstored therein without the continuous provision of electric power.Operation of storage device(s) of non-volatile storage 162 may becontrolled by storage controller 165 (for example, a different storagecontroller than used to operate volatile storage 164), which may receivecommands from processor component 150 and/or other components ofprocessing device 105 to store and/or retrieve information therein, andmay convert those commands between the bus protocols and/or timings bywhich they are received and other bus protocols and/or timings by whichthe storage device(s) of non-volatile storage 162 are coupled to storagecontroller 165. By way of example, one or more storage devices ofnon-volatile storage 162 may be made up of ferromagnetic disk-baseddrives (hard drives) operably coupled to storage controller 165 via adigital serial interface, for instance, in which portions of the storagespace within each such storage device are addressed by reference totracks and sectors. In contrast, commands received by storage controller165 may be conveyed thereto along one or more pairs of digital serialtransmission lines conveying read and write commands in which those sameportions of the storage space within each such storage device areaddressed in an entirely different manner.

Processor component 150 may include at least one processor core 170 toexecute instructions of an executable routine in at least one thread ofexecution. However, processor component 150 may incorporate more thanone of processor cores 170 and/or may employ other processingarchitecture techniques to support multiple threads of execution bywhich the instructions of more than one executable routine may beexecuted in parallel. Cache(s) 172 may include a multilayer set ofcaches that may include separate first level (L1) caches for eachprocessor core 170 and/or a larger second level (L2) cache for multipleones of processor cores 170.

In some embodiments in which processing device 105 includes display 138and/or graphics controller 176, one or more cores 170 may, as a resultof executing the executable instructions of one or more routines,operate controls 125 and/or the display 138 to provide a user interfaceand/or to perform other graphics-related functions. Graphics controller176 may include a graphics processor core (for instance, a graphicsprocessing unit (GPU)) and/or component (not shown) to performgraphics-related operations, including and not limited to, decompressingand presenting a motion video, rendering a 2D image of one or moreobjects of a three-dimensional (3D) model, etc.

Non-volatile storage 162 may store data 130, including executableinstructions 132. In the aforementioned exchanges of data 130 betweenprocessing device 105 and server 110, processing device 105 may maintaina copy of data 130, for instance, for longer term storage withinnon-volatile storage 162. Volatile storage 164 may store encrypted data134 and/or metadata 136. Encrypted data 134 may be made up of at least aportion of data 130 stored within volatile storage 164 in encryptedand/or compressed form according to some embodiments described herein.Executable instructions 132 may make up one or more executable routinessuch as an operating system (OS), device drivers and/or one or moreapplication routines to be executed by one or more processor cores 170of processor component 150. Other portions of data 130 may include datavalues that are employed by one or more processor cores 170 as inputs toperforming various tasks that one or more processor cores 170 are causedto perform by execution of executable instructions 132.

As part of performing the executable instructions 132, one or moreprocessor cores 170 may retrieve portions of executable instructions 132and store those portions within volatile storage 164 in a more readilyexecutable form in which addresses are derived, indirect references areresolved and/or links are more fully defined among those portions in theprocess often referred to as loading. As familiar to those skilled inthe art, such loading may occur under the control of a loading routineand/or a page management routine of an OS that may be among executableinstructions 132. As portions of data 130 (including portions ofexecutable instructions 132) are so exchanged between non-volatilestorage 162 and volatile storage 164, security subsystem 174 may convertthose portions of data 130 between what may be their originaluncompressed and unencrypted form as stored within non-volatile storage162, and a form that is at least encrypted and that may be stored withinvolatile storage 164 as encrypted data 134 accompanied by metadata 136.

Security subsystem 174 may include hardware logic configured orotherwise controlled by security microcode 178 to implement the logic toperform such conversions during normal operation of processing device105. Security microcode 178 may include indications of connections to bemade between logic circuits within the security subsystem 174 to formsuch logic. Alternatively or additionally, security microcode 178 mayinclude executable instructions that form such logic when so executed.Either security subsystem 174 may execute such instructions of thesecurity microcode 178, or security subsystem 174 may be controlled byat least one processor core 170 that executes such instructions.Security subsystem 174 and/or at least one processor core 170 may beprovided with access to security microcode 178 during initialization ofthe processing device 105, including initialization of the processorcomponent 150. Further, security subsystem 174 may include one or moreof the embodiments described herein for unified hardware acceleration ofhash functions.

Security credentials 180 may include one or more values employed bysecurity subsystem 174 as inputs to its performance of encryption ofdata 130 and/or of decryption of encrypted data 134 as part ofperforming conversions there between during normal operation ofprocessing device 105. More specifically, security credentials 180 mayinclude any of a variety of types of security credentials, including andnot limited to public and/or private keys, seeds for generating randomnumbers, instructions to generate random numbers, certificates,signatures, ciphers, and/or the like. Security subsystem 174 may beprovided with access to security credentials 180 during initializationof the processing device 105.

FIG. 11 illustrates an example of a storage medium 1100. Storage medium1100 may comprise an article of manufacture. In some examples, storagemedium 1100 may include any non-transitory computer readable medium ormachine readable medium, such as an optical, magnetic or semiconductorstorage. Storage medium 1100 may store various types of computerexecutable instructions, such as instructions 1102, which may correspondto any embodiment described herein, or to implement the algorithmsdescribed herein and illustrated in flow charts 240, 252, 346, 358, 500,and 600. Examples of a computer readable or machine readable storagemedium may include any tangible media capable of storing electronicdata, including volatile memory or non-volatile memory, removable ornon-removable memory, erasable or non-erasable memory, writeable orre-writeable memory, and so forth. Examples of computer executableinstructions may include any suitable type of code, such as source code,compiled code, interpreted code, executable code, static code, dynamiccode, object-oriented code, visual code, and the like. The examples arenot limited in this context.

FIG. 12 illustrates an embodiment of an exemplary computing architecture1200 suitable for implementing various embodiments as previouslydescribed. In one embodiment, the computing architecture 1200 maycomprise or be implemented as part of an electronic device. Examples ofan electronic device may include those described herein, such aselectroporation delivery system 905 of FIG. 9 and processing device 105of FIG. 10. The embodiments are not limited in this context.

As used in this application, the terms “system” and “component” areintended to refer to a computer-related entity, either hardware, acombination of hardware and software, software, or software inexecution, examples of which are provided by the exemplary computingarchitecture 1200. For example, a component can be, but is not limitedto being, a process running on a processor, a processor, a hard diskdrive, multiple storage drives (of optical and/or magnetic storagemedium), an object, an executable, a thread of execution, a program,and/or a computer. By way of illustration, both an application runningon a server and the server can be a component. One or more componentscan reside within a process and/or thread of execution, and a componentcan be localized on one computer and/or distributed between two or morecomputers. Further, components may be communicatively coupled to eachother by various types of communications media to coordinate operations.The coordination may involve the uni-directional or bi-directionalexchange of information. For instance, the components may communicateinformation in the form of signals communicated over the communicationsmedia. The information can be implemented as signals allocated tovarious signal lines. In such allocations, each message is a signal.Further embodiments, however, may alternatively employ data messages.Such data messages may be sent across various connections. Exemplaryconnections include parallel interfaces, serial interfaces, and businterfaces.

The computing architecture 1200 includes various common computingelements, such as one or more processors, multi-core processors,co-processors, memory units, chipsets, controllers, peripherals,interfaces, oscillators, timing devices, video cards, audio cards,multimedia input/output (I/O) components, power supplies, and so forth.The embodiments, however, are not limited to implementation by thecomputing architecture 1200.

As shown in FIG. 12, the computing architecture 1200 comprises aprocessing unit 1204, a system memory 1206 and a system bus 1208. Theprocessing unit 1204 can be any of various commercially availableprocessors, including without limitation an AMD® Athlon®, Duron® andOpteron® processors; ARM® application, embedded and secure processors;IBM® and Motorola® DragonBall® and PowerPC® processors; IBM and Sony®Cell processors; Intel® Celeron®, Core (2) Duo®, Itanium®, Pentium®,Xeon®, and XScale® processors; and similar processors. Dualmicroprocessors, multi-core processors, and other multi-processorarchitectures may also be employed as the processing unit 1204. Forexample, the unified hardware acceleration for hash functions describedherein may be performed by processing unit 1204 in some embodiments.

The system bus 1208 provides an interface for system componentsincluding, but not limited to, the system memory 1206 to the processingunit 1204. The system bus 1208 can be any of several types of busstructure that may further interconnect to a memory bus (with or withouta memory controller), a peripheral bus, and a local bus using any of avariety of commercially available bus architectures. Interface adaptersmay connect to the system bus 1208 via a slot architecture. Example slotarchitectures may include without limitation Accelerated Graphics Port(AGP), Card Bus, (Extended) Industry Standard Architecture ((E)ISA),Micro Channel Architecture (MCA), NuBus, Peripheral ComponentInterconnect (Extended) (PCI(X)), PCI Express, Personal Computer MemoryCard International Association (PCMCIA), and the like.

The computing architecture 1200 may comprise or implement variousarticles of manufacture. An article of manufacture may comprise acomputer-readable storage medium to store logic. Examples of acomputer-readable storage medium may include any tangible media capableof storing electronic data, including volatile memory or non-volatilememory, removable or non-removable memory, erasable or non-erasablememory, writeable or re-writeable memory, and so forth. Examples oflogic may include executable computer program instructions implementedusing any suitable type of code, such as source code, compiled code,interpreted code, executable code, static code, dynamic code,object-oriented code, visual code, and the like. Embodiments may also beat least partly implemented as instructions contained in or on anon-transitory computer-readable medium, which may be read and executedby one or more processors to enable performance of the operationsdescribed herein.

The system memory 1206 may include various types of computer-readablestorage media in the form of one or more higher speed memory units, suchas read-only memory (ROM), random-access memory (RAM), dynamic RAM(DRAM), Double-Data-Rate DRAM (DDRAM), synchronous DRAM (SDRAM), staticRAM (SRAM), programmable ROM (PROM), erasable programmable ROM (EPROM),electrically erasable programmable ROM (EEPROM), flash memory, polymermemory such as ferroelectric polymer memory, ovonic memory, phase changeor ferroelectric memory, silicon-oxide-nitride-oxide-silicon (SONOS)memory, magnetic or optical cards, an array of devices such as RedundantArray of Independent Disks (RAID) drives, solid state memory devices(e.g., USB memory, solid state drives (SSD) and any other type ofstorage media suitable for storing information. In the illustratedembodiment shown in FIG. 12, the system memory 1006 can includenon-volatile memory 1210 and/or volatile memory 1213. A basicinput/output system (BIOS) can be stored in the non-volatile memory1210.

The computer 1202 may include various types of computer-readable storagemedia in the form of one or more lower speed memory units, including aninternal (or external) hard disk drive (HDD) 1214, a magnetic floppydisk drive (FDD) 1216 to read from or write to a removable magnetic disk1218, and an optical disk drive 1220 to read from or write to aremovable optical disk 1222 (e.g., a CD-ROM, DVD, or Blu-ray). The HDD1214, FDD 1216 and optical disk drive 1220 can be connected to thesystem bus 1208 by a HDD interface 1224, an FDD interface 1226 and anoptical drive interface 1228, respectively. The HDD interface 1224 forexternal drive implementations can include at least one or both ofUniversal Serial Bus (USB) and IEEE 1394 interface technologies.

The drives and associated computer-readable media provide volatileand/or nonvolatile storage of data, data structures, computer-executableinstructions, and so forth. For example, a number of program modules canbe stored in the drives and memory 1210, 1213, including an operatingsystem 1230, one or more application programs 1232, other programmodules 1234, and program data 1236. In one embodiment, the one or moreapplication programs 1232, other program modules 1234, and program data1236 can include, for example, the various applications and/orcomponents to implement the disclosed embodiments.

A user can enter commands and information into the computer 1202 throughone or more wire/wireless input devices, for example, a keyboard 1238and a pointing device, such as a mouse 1240. Other input devices mayinclude microphones, infra-red (IR) remote controls, radio-frequency(RF) remote controls, game pads, stylus pens, card readers, dongles,finger print readers, gloves, graphics tablets, joysticks, keyboards,retina readers, touch screens (e.g., capacitive, resistive, etc.),trackballs, trackpads, sensors, styluses, and the like. These and otherinput devices are often connected to the processing unit 1204 through aninput device interface 1242 that is coupled to the system bus 1208, butcan be connected by other interfaces such as a parallel port, IEEE 1394serial port, a game port, a USB port, an IR interface, and so forth.

A display 1244 is also connected to the system bus 1208 via aninterface, such as a video adaptor 1246. The display 1244 may beinternal or external to the computer 1202. In addition to the display1244, a computer typically includes other peripheral output devices,such as speakers, printers, and so forth.

The computer 1202 may operate in a networked environment using logicalconnections via wire and/or wireless communications to one or moreremote computers, such as a remote computer 1248. The remote computer1248 can be a workstation, a server computer, a router, a personalcomputer, portable computer, microprocessor-based entertainmentappliance, a peer device or other common network node, and typicallyincludes many or all of the elements described relative to the computer1202, although, for purposes of brevity, only a memory/storage device1250 is illustrated. The logical connections depicted includewire/wireless connectivity to a local area network (LAN) 1252 and/orlarger networks, for example, a wide area network (WAN) 1254. Such LANand WAN networking environments are commonplace in offices andcompanies, and facilitate enterprise-wide computer networks, such asintranets, all of which may connect to a global communications network,for example, the Internet.

When used in a LAN networking environment, the computer 1202 isconnected to the LAN 1252 through a wire and/or wireless communicationnetwork interface or adaptor 1256. The adaptor 1256 can facilitate wireand/or wireless communications to the LAN 1252, which may also include awireless access point disposed thereon for communicating with thewireless functionality of the adaptor 1256.

When used in a WAN networking environment, the computer 1202 can includea modem 1258, or is connected to a communications server on the WAN1254, or has other means for establishing communications over the WAN1254, such as by way of the Internet. The modem 1258, which can beinternal or external and a wire and/or wireless device, connects to thesystem bus 1208 via the input device interface 1242. In a networkedenvironment, program modules depicted relative to the computer 1202, orportions thereof, can be stored in the remote memory/storage device1250. It will be appreciated that the network connections shown areexemplary and other means of establishing a communications link betweenthe computers can be used.

The computer 1202 is operable to communicate with wire and wirelessdevices or entities using the IEEE 802 family of standards, such aswireless devices operatively disposed in wireless communication (e.g.,IEEE 802.11 over-the-air modulation techniques). This includes at leastWi-Fi (or Wireless Fidelity), WiMax, and Bluetooth™ wirelesstechnologies, among others. Thus, the communication can be a predefinedstructure as with a conventional network or simply an ad hoccommunication between at least two devices. Wi-Fi networks use radiotechnologies called IEEE 802.11x (a, b, g, n, etc.) to provide secure,reliable, fast wireless connectivity. A Wi-Fi network can be used toconnect computers to each other, to the Internet, and to wire networks(which use IEEE 802.3-related media and functions).

One or more aspects of at least one embodiment described herein may beimplemented by representative instructions stored on a machine-readablemedium which represents various logic within the processor, which whenread by a machine causes the machine to fabricate logic to perform thetechniques described herein. Such representations, known as “IP cores”may be stored on a tangible, machine readable medium and supplied tovarious customers or manufacturing facilities to load into thefabrication machines that actually make the logic or processor. Someembodiments may be implemented, for example, using a machine-readablemedium or article which may store an instruction or a set ofinstructions that, if executed by a machine, may cause the machine toperform a method and/or operations in accordance with the embodiments.Such a machine may include, for example, any suitable processingplatform, computing platform, computing device, processing device,computing system, processing system, computer, processor, or the like,and may be implemented using any suitable combination of hardware and/orsoftware. The machine-readable medium or article may include, forexample, any suitable type of memory unit, memory device, memoryarticle, memory medium, storage device, storage article, storage mediumand/or storage unit, for example, memory, removable or non-removablemedia, erasable or non-erasable media, writeable or re-writeable media,digital or analog media, hard disk, floppy disk, Compact Disk Read OnlyMemory (CD-ROM), Compact Disk Recordable (CD-R), Compact DiskRewriteable (CD-RW), optical disk, magnetic media, magneto-opticalmedia, removable memory cards or disks, various types of DigitalVersatile Disk (DVD), a tape, a cassette, or the like. The instructionsmay include any suitable type of code, such as source code, compiledcode, interpreted code, executable code, static code, dynamic code,encrypted code, and the like, implemented using any suitable high-level,low-level, object-oriented, visual, compiled and/or interpretedprogramming language.

Numerous specific details have been set forth herein to provide athorough understanding of the embodiments. It will be understood bythose skilled in the art, however, that the embodiments may be practicedwithout these specific details. In other instances, well-knownoperations, components, and circuits have not been described in detailso as not to obscure the embodiments. It can be appreciated that thespecific structural and functional details disclosed herein may berepresentative and do not necessarily limit the scope of theembodiments.

Some embodiments may be described using the expression “coupled” and“connected” along with their derivatives. These terms are not intendedas synonyms for each other. For example, some embodiments may bedescribed using the terms “connected” and/or “coupled” to indicate thattwo or more elements are in direct physical or electrical contact witheach other. The term “coupled,” however, may also mean that two or moreelements are not in direct contact with each other, but yet stillco-operate or interact with each other.

Unless specifically stated otherwise, it may be appreciated that termssuch as “processing,” “computing,” “calculating,” “determining,” or thelike, refer to the action and/or processes of a computer or computingsystem, or similar electronic computing device, that manipulates and/ortransforms data represented as physical quantities (e.g., electronic)within the computing system's registers and/or memories into other datasimilarly represented as physical quantities within the computingsystem's memories, registers or other such information storage,transmission or display devices. The embodiments are not limited in thiscontext.

It should be noted that the methods described herein do not have to beexecuted in the order described, or in any particular order. Moreover,various activities described with respect to the methods identifiedherein can be executed in serial or parallel fashion.

Although specific embodiments have been illustrated and describedherein, it should be appreciated that any arrangement calculated toachieve the same purpose may be substituted for the specific embodimentsshown. This disclosure is intended to cover any and all adaptations orvariations of various embodiments. It is to be understood that the abovedescription has been made in an illustrative fashion, and not arestrictive one. Combinations of the above embodiments, and otherembodiments not specifically described herein will be apparent to thoseof skill in the art upon reviewing the above description. Thus, thescope of various embodiments includes any other applications in whichthe above compositions, structures, and methods are used.

Although the subject matter has been described in language specific tostructural features and/or methodological acts, it is to be understoodthat the subject matter defined in the appended claims is notnecessarily limited to the specific features or acts described above.Rather, the specific features and acts described above are disclosed asexample forms of implementing the claims.

What is claimed is:
 1. An electroporation delivery system, comprising:an electrocardiogram operatively connected to a processing device and amemory; one or more sensors operatively connected to theelectrocardiogram for measuring electrical activity QRS complex of apatient's heart; and one or more electrodes for treatment in, at, ornear the patient's heart, the one or more electrodes operativelyconnected to a pulse delivery mechanism; wherein the electroporationdelivery system is configured to determine whether an electroporationpulse is deliverable to a patient based on the electrocardiogram.
 2. Theelectroporation delivery system according to claim 1, wherein theprocessing device is configured to execute the following steps:measuring and averaging approximately 30 initial heartbeat durations ofthe patient's heart; calculating a rolling average by averaging a seriesof four heartbeat durations; and comparing the rolling average to theaveraged initial heartbeat durations including a standard deviation;wherein if the rolling average is equal to the average initial heartbeatdurations within the standard deviation, delivering the electroporationpulse during a fifth heartbeat duration following the averaged series offour heartbeat durations, and if the rolling average is not equal to theaverage initial heartbeat durations within the standard deviation, notdelivering the electroporation pulse during the fifth heartbeat durationfollowing the averaged series of four heartbeat durations.
 3. Theelectroporation delivery system according to claim 1, wherein theprocessing device is configured to execute the following steps:calculating a rolling average by averaging a series of four heartbeatdurations; setting the rolling average to a heartbeat average includinga standard deviation; and comparing the rolling average to a fifthheartbeat duration following the averaged series of four heartbeatdurations; wherein if the fifth heartbeat duration following theaveraged series of four heartbeat durations is equal to the rollingaverage within the standard deviation, delivering an electroporationpulse during a sixth heartbeat duration following the fifth heartbeatduration, and if the fifth heartbeat duration following the averagedseries of the four heartbeat durations is not equal to the rollingaverage within the standard deviation, not delivering theelectroporation pulse during the sixth heartbeat duration following thefifth heartbeat duration.
 4. The electroporation delivery systemaccording to claim 3, wherein delivery of the electroporation pulseduring the sixth heartbeat duration occurs at a time determined by theaveraged series of four heartbeat durations divided by two after a Qwave of the QRS complex of the sixth heartbeat duration.
 5. Theelectroporation delivery system according to claim 1, wherein theprocessing device is configured to execute the following steps:measuring and averaging approximately 30 initial R wave amplitudes inthe QRS complex of the patient's heart; calculating a rolling average byaveraging a series of four R wave amplitudes; and comparing the rollingaverage to the average initial R wave amplitudes including a standarddeviation; wherein if the rolling average is equal to the averageinitial R wave amplitudes within the standard deviation, delivering theelectroporation pulse during a fifth heartbeat duration following theaveraged series of four R wave amplitudes, and if the rolling average isnot equal to the average initial R wave amplitudes within the standarddeviation, not delivering the electroporation pulse during the fifthheartbeat duration following the averaged series of four R waveamplitudes.
 6. The electroporation delivery system according to claim 1,wherein the processing device is configured to execute the followingsteps: calculating a rolling average by averaging a series of four Rwave amplitudes in the QRS complex of the patient's heart; setting therolling average to the averaged R wave amplitudes including a standarddeviation; and comparing the rolling average to a fifth R wave amplitudeof a fifth heartbeat duration following the averaged series of four Rwave amplitudes; wherein if the fifth R wave amplitude following theaveraged series of four R wave amplitudes is equal to the rollingaverage within the standard deviation, delivering the electroporationpulse during a sixth heartbeat duration following the fifth R waveamplitude, and if the fifth R wave amplitude following the averagedseries of the four R wave amplitudes is not equal to the rolling averagewithin the standard deviation, not delivering the electroporation pulseduring the sixth heartbeat duration following the fifth R waveamplitude.
 7. The electroporation delivery system according to claim 1,further comprising one or more signal filters for extracting at leastone of an R wave and a T wave of the QRS complex; wherein theelectroporation pulse is deliverable in response to a positive value ofthe R wave and a negative value of the T wave output from the one ormore filters; wherein the electroporation pulse is not deliverable inresponse to the positive value of the R wave and a positive value of theT wave output from the one or more filters; and wherein theelectroporation pulse is deliverable in response to the R wave beingwithin 70 ms and the negative value of the T wave output from the one ormore filters.
 8. The electroporation delivery system according to claim1, wherein pacing of the patient's heart is adjustable forelectroporation pulse delivery by induced pacing, including thefollowing steps: pacing a portion of the patient's heart; detecting anevoked potential, wherein if no evoked potential is detected, the pacingof the portion of the patient's heart is continued and noelectroporation pulse is delivered, and: in response to detecting evokedpotential, determining if the detection occurs during a vulnerableperiod of a T wave; wherein in response to the detection occurringduring the vulnerable period of the T wave, the pacing of the portion ofthe patient's heart is continued and no electroporation pulse isdelivered; and wherein in response to the detection not occurring duringthe vulnerable period of the T wave, delivering the electroporationpulse.
 9. The electroporation delivery system according to claim 1,wherein pacing of the patient's heart is adjustable for electroporationpulse delivery by continuous pacing, including the following steps: (a)sending a continuous pacing signal to the patient's heart to maintainthe heart in a contracted state; (b) during the continuous pacing,delivering one or more electroporation pulses; and (c) monitoring heartrhythms of the patient for irregularities, wherein in response todetecting an irregularity, pacing the patient's heart to a normalrhythm; and wherein in response to detecting a regular heartbeat,repeating steps (a), (b), and (c) if additional treatment is needed. 10.The electroporation delivery system according to claim 1, whereinelectroporation pulse delivery is paused for monitoring theelectrocardiogram for regular heart rhythms.
 11. The electroporationdelivery system according to claim 1, wherein an electroporation pulseshape is at least one of square-shaped and defibrillation-like shaped,and wherein the electroporation pulse shape is at least one of monopolarand bipolar.
 12. The electroporation delivery system according to claim1, wherein the electroporation delivery system is operational fortreating at least one of atrial fibrillation and cancer disposed in, at,or near the heart.
 13. A method for delivering an electroporation pulseby an electroporation delivery system for treatment in, at, or near apatient's heart, comprising: measuring electrical activity QRS complexof the patient's heart by an electrocardiogram and one or more sensorsoperatively connected to a processing device and a memory; calculatingby the processing device a rolling average by averaging a series of fourheartbeat parameters, and comparing the rolling average to a determinedvalue; and delivering the electroporation pulse by one or moreelectrodes operatively connected to a pulse delivery mechanism of theelectroporation delivery system in response to the rolling average beingequal to the determined value.
 14. The method according to claim 13,wherein the determined value is determined by measuring and averagingapproximately 30 initial heartbeat parameters of a patient's heart; andincluding a standard deviation to the average initial heartbeatparameters.
 15. The method according to claim 13, wherein the determinedvalue is a fifth heartbeat parameter following the averaged series offour heartbeat parameters, and the rolling average is set to a heartbeataverage including a standard deviation.
 16. The method according toclaim 15, further comprising delivering the electroporation pulse duringa fifth heartbeat duration following the averaged series of fourheartbeat parameters; and not delivering the electroporation pulseduring the fifth heartbeat duration following the averaged series offour heartbeat parameters in response to the rolling average notequaling the determined value.
 17. The method according to claim 15,further comprising delivering the electroporation pulse during a sixthheartbeat duration following a fifth heartbeat duration; and notdelivering the electroporation pulse during the sixth heartbeat durationfollowing the fifth heartbeat duration in response to the fifthheartbeat parameter not equaling the rolling average within the standarddeviation.
 18. The method according to claim 13, wherein a heartbeatparameter is at least one of a heartbeat duration and an R waveamplitude.
 19. The method according to claim 13, further comprisingadjusting a pace of the patient's heart at least one of before, during,and after delivering the electroporation pulse.
 20. A system fordelivering an electroporation pulse by an electroporation deliverysystem for treatment in, at, or near a patient's heart, the system beingconfigured to execute the following steps: measuring electrical activityQRS complex of the patient's heart by an electrocardiogram and one ormore sensors operatively connected to a processing device and a memory;calculating by the processing device a rolling average by averaging aseries of four heartbeat parameters, and comparing the rolling averageto a determined value; and delivering an electroporation pulse by one ormore electrodes operatively connected to a pulse delivery mechanism ofthe electroporation delivery system in response to the rolling averagebeing equal to the determined value.